Drugs Aid Metastatic RCC Outcomes

Sunitinib and sorafenib prolong progression-free survival but do not decrease overall mortality risk.

Two relatively new oral agents can improve outcomes for patients with metastatic renal cell carcinoma (RCC), according to recent reports. The drugs, sunitinib and sorafenib, inhibit enzymes that promote angiogenesis and thus may act by disrupting tumor vasculature.

One report describes a study comparing sunitinib and interferon alfa in 750 patients with previously un-treated clear-cell metastatic RCC. Researchers led by Robert J. Motzer, MD, of Memorial Sloan-Kettering Cancer Center in New York, found that median progression-free survival was significantly longer in sunitinib recipients than in patients who received interferon alfa (11 vs. 5 months), which corresponds to a 58% decrease in the risk of disease progression associated with sunitinib use, according to a report in the New England Journal of Medicine (2007;356:115-124). Sunitinib was associated with a significantly higher objective response rate than was interferon alfa (31% vs. 6%).

The proportion of patients with grade 3 or 4 treatment-related fatigue was significantly higher in the interferon alfa group (12% vs. 7%), but the sunitinib group had higher rates of grade 3 diarrhea (5% vs. 0%), vomiting (4% vs. 1%), and hypertension (8% vs. 1%). Sunitinib-treated patients reported a better quality of life than the interferon alfa group.

In the same issue (pp. 125-134), Bernard Escudier, MD, of the Institut Gustave Roussy in Villejuif, France, and his colleagues reported that sorafenib significantly increased progression-free survival compared with placebo (5.5 vs. 2.8 months), which translated into a 56% decrease in the risk of disease progression. With respect to overall survival—the primary end point of the study—sorafenib lowered death risk by a nonsignificant 28%.

The finding comes from a study of 903 patients with clear-cell metastatic RCC that were resistant to standard therapy. The median duration of treatment was 23 weeks in the sorafenib group and 12 weeks in the placebo arm. The proportion of patients who discontinued treatment because of adverse events was similar in both groups (10% and 8% in the sorafenib and placebo groups, respectively). Serious adverse events leading to hospitalization or death occurred in 154 patients receiving sorafenib (34%) and in 110 patients receiving placebo (24%).

In an accompanying editorial, James Brugarolas, MD, PhD, of the Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center in Dallas, observed: “It will be important to evaluate how these drugs work through the analysis of both responsive and resistant tumors.”